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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992-11-24 to 1993-03-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name: Cumylperoxyneodecanoate
- Brand name: Trigonox 99-C75
- Batch No.: 0509207222002
- Purity: 75% in aromatic free mineral spirit (CAS No.: 31807-55-3 and 26748-47-0)
- Storage: freezer

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
An appropriate quantity of the test material, as supplied by the Sponsor, was dispensed on the day of dosing.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield S.P.F. Rabbits, Broadway Farm, Froxfield, Hampshire, England
- Age at study initiation: Animals were approximately 4 months old
- Weight at study initiation: 3.35 - 3.60 kg
- Housing: The animals were individually housed in suspended stainless steel cages mounted in mobile batteries. The cages were fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent paper which was changed regularly.
- Diet (e.g. ad libitum): ad libitum; commercially available standard pelleted rabbit diet (S.Q.C. Rabbit Diet, Special Diets Services Limited, Witham, Essex, England).
- Water (e.g. ad libitum): ad libitum; tap water taken from the public supply; in England the supply and quality of this water is governed by Department of the Environment regulations.
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 20 °C
- Humidity (%): 52 - 60%
- Air changes (per hr): 15 complete air changes per hour without re-circulation
- Photoperiod (hrs dark / hrs light): electric time-switches operated a lighting cycle of 12 hours of artificial light per day

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a single dose (0.5 mL) was applied directly to the skin
Duration of treatment / exposure:
4 hours exposure period
Observation period:
1, 24, 48, 72 hours after removal of the bandages. Additional observation of persistent effects of treatment were made 6, 9, 12 and 15 days after treatment.
Number of animals:
3.
A single animal was initially treated. In the absence of a severe irritation response in this sentinel animal, the remaining two animals were committed to the study.
Details on study design:
TEST SITE
- Area of exposure: 6 x 6 cm
- Type of wrap if used: Test material was covered by an unmedicated gauze patch which was held in place on the place on the left test site by strips of Blenderm (Community Care Products, 3M Health Care, Loughborough, England). Pads of cotton whool and elasticated bandage were used to protect the patches and ensure good contact between the skin and the test material.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treatment sites were gently washed with warm water and dried with paper towels to remove excess test material adhering to the skin.

OBSERVATION TIME POINTS
Assessment of skin irritation responses at the control and treated test sites were made 1, 24, 48 and 72 hours after removal of the bandages. Additional observations of persistent effects of treatment were made 6, 9, 12 and 15 days after treatment.

SCORING SYSTEM:
- Method of calculation:
Reactions of the test sites were assessed according to the criteria of Draize (1959) (for details see Table 1 in box 'Any other information on material and methods').

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Well-defined or moderate erythema and very slight to moderate eedema were observed in two rabbits during the first 72 hours following bandage removal. Loss of elasticity was observed in both of these rabbits during the first week of observation. The area affected by these changes extended 2-3 cm beyond the test site of one of these rabbits. On the sixth day, very slight erythema and edema were observed, with the addition of exfoliation. On the ninth and twelfth days, exfoliation was still present in both animals. The test sites of these two animals were overtly normal on the 15th day.
The remaining rabbit showed very slight erythema during the first 72 hours following bandage removal. Very slight edema was also observed at the one-hour examination. Loss of elasticity was observed at 24-hour examination, and persisted until the 12th day. Exfoliation was evident during the latter part of the first week of observation. The test site of this animal was overtly normal on the fifteenth day after treatment.
The test sites of all three animals were sticky to touch at the one and 24-hour examinations. The effect was considered to have been caused by residual dose material and adhering to the skin after the washing procedure. This occurrence did not affect the assessment of the skin responses.
The control site of each animal did not show any response to the control procedure.
The mean values for erythema in two animals and edema in one animal, recorded 24, 48 and 72 hours after treatment, equaled or exceeded the EEC limit values considered to indicate a significant inflammatory response to treatment.

Mean Values for erythema and oedema are summed up in table 2 in box 'Any other information on results incl. tables'.

Any other information on results incl. tables

Table 2: Mean values for erythema and oedema 24, 48, 72 hours after treatment

Animal number and sex Erythema* Oedema*
Test Control Test Control
23TJ 811F 3.0 0.0 2.0 0.0
23TJ 816F 2.0 0.0 1.3 0.0
23TJ 823F 1.0 0.0 0.0 0.0

* Values based on criteria documented in Table 1 in box 'Any other information on material and methods'.

Table 3: Scoring of irritance responses*

Test site: 0.5 mL Trigonox 99 -C75

Control site: No treatment

both: semioccluded for 4 hours

    Score after removal of dressings
Animal number and sex Type of Response 1 hour 24hour 48 hour 72 hours
Test site Control site Test site Control site Test site Control site Test site Control site
23TJ 811F Erythema 3 0 3 0 3 0 3 0
STW STW TW TW  
Oedema 3 0 2 0 2 0 2 0
23TJ 816F Erythema 2 0 2 0 2 0 2 0
ST ST T T  
Oedema 2 0 2 0 1 0 1 0
23TJ 823F# Erythema 1 0 1 0 1 0 1 0
S ST TX TX  
Oedema 1 0 0 0 0 0 0 0

* Criteria documented in Table 1 in box 'Any other information on material and methods'.

# Sentinel animal

S Sticky to touch

T Loss of elasticity

W Area affected extends to 2 -3 cm beyond test site/application site

X Exfoliation

Table 4 : Scoring of irritance response*

Test site: 0.5 mL Trigonox 99 -C75

Control site: No treatment

both: semioccluded for 4 hours

    Score after removal of dressings
Animal number and sex Type of Response 6 days 9 days 12 days 15 days
Test site Control site Test site Control site Test site Control site Test site Control site
23TJ 811F Erythema 1 0 0 0 0 0 0 0
TWX WX X  
Oedema 1 0 0 0 0 0 0 0
23TJ 816F Erythema 2 0 0 0 0 0 0 0
TX X X  
Oedema 1 0 0 0 0 0 0 0
23TJ 823F# Erythema 0 0 0 0 0 0 0 0
TX T T  
Oedema 0 0 0 0 0 0 0 0

* Criteria documented in Table 1 (in box "Any other information on material and methods").

# Sentinel animal

S Sticky to touch

T Loss of elasticity

W Area affected extends to 2 -3 cm beyond test site/application site

X Exfoliation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results and in accordance to the CLP regulation no classification for skin irritation is warranted.
Executive summary:

In a primary dermal irritation study according to guideline OECD 404, 3 female New Zealand White rabbits (4 months old, 3.35 - 3.60 kg) were dermally exposed to 0.5 mL of Trigonox 99 -C75 to the closely-clipped dorsal (6 x 6 cm) of the left site. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 15 days.

Well-defined or moderate erythema and very slight to moderate edema were observed in two rabbits during the first 72 hours following bandage removal. Loss of elasticity was observed in both of these rabbits during this time. On the sixth day very slight erythema and edema and loss of elasticity were observed, with the addition of exfoliation. On the ninth and twelfth days, exfoliation was still present in both animals. The remaining rabbit showed very slight erythema during the first 72 hours following bandage removal. Very slight edema was also observed at the one-hour examination. Loss of elasticity was observed at the 24-hour examination and persisted until the 12th day. Exfoliation was evident during the latter part of the first week of observation. The test sites of all animals were overtly normal on the 15th day after treatment.

In this study, Trigonox 99 -C75 is not a dermal irritant based on CLP criteria.